Medication Summary
Therapeutic approaches to anemia include the use of blood and blood products, immunotherapies, hormonal/nutritional therapies, and adjunctive therapies. The goal of therapy in acute anemia is to restore the hemodynamics of the vascular systems and to replace lost red blood cells. To achieve this, the practitioner may use mineral and vitamin supplements, blood transfusions, vasopressors, histamine (H2) antagonists, and glucocorticosteroids.
Documentation of the etiology of anemia is essential in the selection of therapy. Not all microcytic anemias are caused by iron deficiency; some are iron-overloading disorders. Similarly, not all megaloblastic anemias are associated with either vitamin B12 deficiency or folic acid deficiency. Hereditary hemolytic disorders do not improve with corticosteroid therapy.
Blood and Blood Products
Class Summary
Correction of acute anemia often requires blood and/or blood products. With significant ongoing hemorrhage or hemolysis, transfusion of blood alone is insufficient. Nonetheless, providing timely transfusion to restore hemoglobin to safe levels can prevent major complications of acute anemia.
Packed red blood cells (PRBCs)
Packed red blood cells (PRBCs) are used preferentially to whole blood, since they limit volume, immune, and storage complications. PRBCs have 80% less plasma, are less immunogenic, and can be stored about 40 days (versus 35 d for whole blood). PRBCs are obtained after centrifugation of whole blood. Leukocyte-poor PRBCs are used in patients who are transplant candidates/recipients and in those with prior febrile transfusion reactions. Washed or frozen PRBCs are used in individuals with hypersensitivity transfusion reactions.
Fresh frozen plasma
Fresh frozen plasma (FFP) contains coagulation factors, as well as protein C and protein S. Its uses include the treatment of coagulopathies and thrombotic thrombocytopenic purpura (TTP) and the reversal of warfarin. FFP does not transmit infections.
Cryoprecipitate
This agent is used for the treatment of Von Willebrand disease. It contains fibrinogen, factor VIII, and von Willebrand factor and can be used in lieu of factor VIII concentrate if the latter is unavailable.
Platelets
Patients who are thrombocytopenic and have clinical evidence of bleeding should receive a platelet transfusion. Patients with platelet counts of less than 10,000/mcL are at risk for spontaneous cerebral hemorrhage and require a prophylactic transfusion.
The preferred treatment for TTP and hemolytic-uremic syndrome is large-volume plasmapheresis with FFP replacement. Immune thrombocytopenic purpura (ITP) is rarely treated with transfusion, as the transfused platelets are destroyed rapidly. In stable patients, initial treatment is with prednisone. High-dose immunoglobulin and splenectomy are very effective treatments.
Factor IX (BeneFix, Mononine)
Hemophilia B is treated with factor IX concentrate. Recombinant factor IX currently is undergoing clinical trials (the current treatment is FFP or prothrombin-rich plasma concentrate).
Recombinant factor VIII (Advate, Helixate FS, Xyntha)
This is used to treat hemophilia A.
Iron Products
Class Summary
Iron salts are used to provide adequate iron for hemoglobin synthesis and to replenish body stores of iron. Iron is administered prophylactically during pregnancy because of the anticipated requirements of the fetus and the losses that occur during delivery.
Ferrous sulfate (MyKidz Iron 10, Fer-Iron, Slow-FE)
Mineral supplements are used to provide adequate iron for hemoglobin synthesis and to replenish body stores of iron. Iron is administered prophylactically during pregnancy because of the anticipated requirements of the fetus and the losses that occur during delivery.
Carbonyl iron (Feosol, Iron Chews, Icar)
Carbonyl iron is used as a substitute for ferrous sulfate. It has a slower release of iron and is more expensive than ferrous sulfate. The slower release affords the agent greater safety if ingested by children. On a milligram-for-milligram basis, it is 70% as efficacious as ferrous sulfate. Claims are made that there is less gastrointestinal (GI) toxicity, prompting use when ferrous salts are producing intestinal symptoms and in patients with peptic ulcers and gastritis. Tablets are available containing 45 mg and 60 mg of iron.
Ferric citrate (Auryxia)
Ferric iron is reduced from the ferric to the ferrous form by ferric reductase in the GI tract. After transport through the enterocytes into the blood, oxidized ferric iron circulates bound to the plasma protein transferrin, and can be incorporated into hemoglobin. Ferric citrate 1 g is equivalent to ferric iron 210 mg. It is indicated in adults with iron deficiency anemia who have CKD and are not on dialysis.
Iron dextran complex (INFeD, Dexferrum)
Iron dextran complex replenishes depleted iron stores in the bone marrow, where it is incorporated into hemoglobin. Parenteral use of iron-carbohydrate complexes has caused anaphylactic reactions, and its use should be restricted to patients with an established diagnosis of iron deficiency anemia whose anemia is not corrected with oral therapy.
The required dose can be calculated (3.5 mg iron/g of hemoglobin) or obtained from tables in the prescribing information. For IV use, this agent may be diluted in sterile 0.9% NaCl. Do not add to solutions containing medications or parenteral nutrition solutions.
Ferric carboxymaltose (Injectafer)
Ferric carboxymaltose is a nondextran IV colloidal iron hydroxide in complex with carboxymaltose, a carbohydrate polymer that releases iron. It is indicated for iron deficiency anemia (IDA) in adults who have intolerance or an unsatisfactory response to oral iron. It is also indicated for IDA in adults with non-dialysis-dependent chronic kidney disease.
Vitamins
Class Summary
Vitamins are used to meet necessary dietary requirements and are used in metabolic pathways, as well as DNA and protein synthesis.
Cyanocobalamin (vitamin B12) and folic acid are used to treat megaloblastic and macrocytic anemias secondary to deficiency. Both vitamin B12 and folic acid are required for synthesis of purine nucleotides and metabolism of some amino acids. Each is essential for normal growth and replication. Deficiency of either cyanocobalamin or folic acid results in defective DNA synthesis and cellular maturation abnormalities. Consequences of deficiency are most evident in tissues with high cell turnover rates (eg, hematopoietic system).
Vitamin K deficiency causes elevation of prothrombin time and is commonly seen in patients with liver disease.
Cyanocobalamin ( Calo-Mist, Ener-B, Nascobal)
Deoxyadenosylcobalamin and hydroxocobalamin are active forms of vitamin B12 in humans. Microbes synthesize vitamin B12, but humans and plants do not. Vitamin B12 deficiency may result from intrinsic factor (IF) deficiency (pernicious anemia), partial or total gastrectomy, or diseases of the distal ileum.
Folic acid (Folvite)
Folic acid is an essential cofactor for enzymes used in the production of red blood cells (RBCs).
Vitamin K
A decrease in levels of vitamin K–dependent factors (II, VII, IX, X, protein C, protein S) can lead to bleeding. Vitamin K is also used to treat hemorrhagic disease of the newborn, warfarin-induced bleeding, and hypothrombinemia from other causes (eg, antibiotic, aspirin).
Electrolyte Supplements
Class Summary
Serum potassium levels can fall during therapy for severe cobalamin or folate deficiency and can lead to sudden death. Therefore, potassium supplements may be indicated.
Potassium Chloride (K-Tab, Klor-Con, microK, Epiklor)
Essential for transmission of nerve impulses, contraction of cardiac muscle, maintenance of intracellular tonicity, skeletal and smooth muscles, and maintenance of normal renal function. Gradual potassium depletion occurs via renal excretion, through GI loss or because of low intake.
Depletion usually results from diuretic therapy, primary or secondary hyperaldosteronism, diabetic ketoacidosis, severe diarrhea, if associated with vomiting, or inadequate replacement during prolonged parenteral nutrition.
Potassium depletion sufficient to cause 1 mEq/L drop in serum potassium requires a loss of about 100 to 200 mEq of potassium from the total body store.
Vasopressors
Class Summary
These drugs decrease portal circulation pressure by diminishing blood flow due to vasoconstriction. The major indication is variceal bleeding.
Vasopressin (Pitressin)
Vasopressin causes vasoconstriction of vascular smooth muscles and increases water permeability and reabsorption in the collecting tubules. It decreases portal pressure in patients with portal hypertension.
Histamine (H2) Antagonists
Class Summary
These agents produce a blockade of H2 receptors.
Cimetidine (Tagamet)
The primary indication is to reduce symptoms and accelerate healing of gastric ulcers. In the acutely bleeding patient, it has limited benefit.
Ranitidine (Zantac)
Ranitidine inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen ion concentrations.
Famotidine (Pepcid)
Famotidine competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.
Nizatidine (Axid)
Nizatidine competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.
Glucocorticoids
Class Summary
These agents are used to treat idiopathic and acquired autoimmune hemolytic anemias.
Prednisone
Glucocorticoids inhibit phagocytosis of antibody-covered platelets. Treatment of ITP during pregnancy is conservative unless the condition is severe. For severe cases, use the lowest dose of glucocorticoids. In neonates, if the platelet count drops below 50,000-75,000 platelets/µL, consider prednisone and exchange transfusions and immunoglobulin.
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Anemia. Decreased production of red blood cells is suggested in certain patients with anemia. Bone marrow biopsy specimen allows categorization of patients with anemia without evidence of blood loss or hemolysis into 3 groups: aplastic or hypoplastic disorder, hyperplastic disorder, or infiltration disorder. Each category and its associated causes are listed in this image.
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Microcytic anemia.
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Peripheral smear showing classic spherocytes with loss of central pallor in the erythrocytes.
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Bone marrow aspirate containing increased numbers of plasma cells.
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Bone marrow aspirate showing erythroid hyperplasia and many binucleated erythroid precursors.
Tables
Condition |
Serum Iron |
Total Iron-Binding Capacity (TIBC) |
Bone Marrow Iron |
Comment |
Iron deficiency |
↓ |
↑ |
0 |
Responsive to iron therapy |
Chronic inflammation |
↓ |
↓ |
++ |
Unresponsive to iron therapy |
Thalassemia major |
↑ |
N |
++++ |
Reticulocytosis and indirect bilirubinemia |
Thalassemia minor |
N |
N - ↓ |
++ |
Elevation of fetal hemoglobin and Hb A2, target cells, and poikilocytosis |
Lead poisoning |
N |
N |
++ |
Basophilic stippling of RBCs |
Sideroblastic |
↑ |
N |
++++ |
Ring sideroblasts in marrow |
Hemoglobin |
N |
N |
++ |
Hemoglobin electrophoresis |
↓ = decreased; ↑ = increased; 0 = absent; +'s indicate the amount of stainable iron in bone marrow specimens, on a scale of 0-4; N = normal. |
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Megaloblastic bone marrow |
Deficiency of vitamin B12 |
Deficiency of folic acid |
|
Drugs affecting deoxyribonucleic acid (DNA) synthesis |
|
Inherited disorders of DNA synthesis |
|
Nonmegaloblastic bone marrow |
Liver disease |
Hypothyroidism and hypopituitarism |
|
Accelerated erythropoiesis (reticulocytes) |
|
Hypoplastic and aplastic anemia |
|
Infiltrated bone marrow |
Macrocyte |
Larger than normal (>8.5 µm diameter). See Table 2. |
Microcyte |
Smaller than normal (< 7 µm diameter). See Table 1. |
Hypochromic |
Less hemoglobin in cell. Enlarged area of central pallor. See Table 1. |
Spherocyte |
Loss of central pallor, stains more densely, often microcytic. Hereditary spherocytosis and certain acquired hemolytic anemias |
Target cell |
Hypochromic with central "target" of hemoglobin. Liver disease, thalassemia, hemoglobin D, and postsplenectomy |
Leptocyte |
Hypochromic cell with a normal diameter and decreased MCV. Thalassemia |
Elliptocyte |
Oval to cigar shaped. Hereditary elliptocytosis, certain anemias (particularly vitamin B12 and folate deficiency) |
Schistocyte |
Fragmented helmet- or triangular-shaped RBCs. Microangiopathic anemia, artificial heart valves, uremia, and malignant hypertension |
Stomatocyte |
Slitlike area of central pallor in erythrocyte. Liver disease, acute alcoholism, malignancies, hereditary stomatocytosis, and artifact |
Tear-shaped RBCs |
Drop-shaped erythrocyte, often microcytic. Myelofibrosis and infiltration of marrow with tumor. Thalassemia |
Acanthocyte |
Five to 10 spicules of various lengths and at irregular intervals on surface of RBCs |
Echinocyte |
Evenly distributed spicules on surface of RBCs, usually 10-30. Uremia, peptic ulcer, gastric carcinoma, pyruvic kinase deficiency, and preparative artifact |
Sickle cell |
Elongated cell with pointed ends. Hemoglobin S and certain types of hemoglobin C and l |
|
Hereditary |
Acquired |
Intracorpuscular defect |
Hereditary spherocytosis Hereditary elliptocytosis Hemoglobinopathies Thalassemias Congenital dyserythropoietic anemias Hereditary RBC enzymatic deficiencies Rarer hereditary abnormalities |
Vitamin B12 and folic acid deficiency Paroxysmal nocturnal hemoglobinuria Severe iron deficiency |
Extracorpuscular defect |
|
Physical agents: Burns, cold exposure Traumatic: Prosthetic heart valves, march hemoglobinuria, disseminated intravascular coagulation (DIC), graft rejection Chemicals: Drugs and venoms Infectious agents: Malaria, toxoplasmosis, mononucleosis, hepatitis, primary atypical pneumonia, clostridial infections, bartonellosis, leishmaniasis Hepatic and renal disease Collagen vascular disease Malignancies: Particularly hematologic neoplasia Transfusion of incompatible blood Hemolytic disease of the newborn Cold hemagglutinin disease Autoimmune hemolytic anemia Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) |
